Prof. Thajasvarie Naicker: “Angiogenesis in HIV Associated Preeclampsia”

Abstract

• Introduction: Preeclampsia (PE) is associated with inadequate uteroplacental perfusion and resultant endothelial dysfunction. This hypoxic microenvironment creates an imbalance of circulating angiogenic [vascular endothelial growth factor (VEGF); placental growth factor (PIGF)] and antiangiogenic factors [soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng)]. Lymphatic vessels transport lymph fluid, proteins, and other cells that leak into tissues from the bloodstream and return them to the circulatory system. Both blood and lymphatic capillaries are lined by a monolayer of endothelial cells of mesodermal origin. In view of the paradoxical effect of HIV infection on PE development, this study examines angiogenesis (Flt-l, sFlt-1 and Eng) and lymphangiogenesis (lymphatic vessel endothelial -LYVE-1 and podoplanin) in the HIV endemic area of KwaZulu-Natal, South Africa.
• Materials and Methods: Placental tissue was obtained from normotensive and preeclamptic women and further stratified by HIV status. Conventional immunohistochemistry performed using VEGF, PlGF, sFlT-1, Eng, LYVE-1 and podoplanin antibodies. Immunostaining within conducting (stem) and exchange (intermediate/terminal) villi at term were morphometrically analysed using the Zeiss Axiovision software.
• Results: Flt-l, sFlt-1 and Eng was strongly immunolocalised in the endothelial, syncytio and cyto- trophoblast cells as well as the extravillous trophoblast cells. A significant difference was noted in Eng immunoexpression between exchange (p=0.02) and conducting villi (p< 0.001), with a higher immunoexpression in both villi types of the preeclamptic compared to the normotensive groups. However, a lack of statistical significance was noted on the effect of HIV status on Flt-1 and sFlt-1 immunoexpression in both exchange and stem villi. A significant difference was observed in the exchange villi for Flt-1 and sFlt-1 immunoexpression (p < 0.003) between the preeclamptic vs the normotensive groups, rather than stem villi. Irrespective of pregnancy type (normotensive versus PE), there was no significant effect of HIV status on Flt-1, sFlt-1 and Eng immunoexpression within the exchange and conducting villi. Podoplanin was immunolocalized in a reticular-like stromal complex within the exchange and conducting villi compared to the endothelial localization of LYVE. Both LYVE-1 and podoplanin were upregulated in HIV+ vs. HIV- groups regardless of pregnancy and villi type. Both markers were down regulated in PE compared to normotensive pregnancies.
• Conclusion: In conclusion, the paradigm shift of an imbalance in the angiogenic and lymphangiogenic transfer predominates in PE pregnancies. In PE comorbid with HIV infection, HIV utilizes its accessory proteins to exploit VEGF’s effect. Anti-retroviral therapy leads to endothelial dysfunction and decreased nitric oxide that induce endothelial oxidative stress. Moreover, HAART re-constitutes the immune response in PE, thereby predisposing women to PE development. Further large-scale studies are urgently required to investigate the effect of the duration of HAART on PE development.

Curriculum Vitae

Professor Thajasvarie Naicker holds a Doctor in Philosophy degree (PhD) in Obstetrics & Gynaecology from the University of KwaZulu-Natal (UKZN), South Africa. In addition she is a qualified microscopist and a Fellow (FRMS) of the Royal Microscopy Society, United Kingdom. She is a Professor within the Nelson R Mandela School of Medicine, College of Health Sciences in UKZN. Prof Naicker is the Research Head of Optics & Imaging Centre, Doris Duke Medical Research Institute and Chair of the Placental Research Group, the largest such group on the African Continent. Her research interests are in pre-eclampsia pathogenesis, HIV associated hypertension in pregnancy and paediatric nephropathy. Due to her experience in electron microscopy she has co-authored a number of papers involving ultrastructure. She is recognized as an established scientific researcher and has published over 324 scientific papers in journals and conference proceedings. She serves on the Editorial Board of journals, reviewer and has been invited as the plenary speaker at meetings. She has received a number of Scholarships. More recently, she received the Africa Oxford University Research Initiative for capacity development in Africa. Prof Naicker has a track record of carrying out capacity development workshops in Africa where she teaches academic staff the latest scientific/research methodologies in medicine. Additionally, she has an excellent track record of supervision having supervised 58 postgraduate degrees (masters and PhD level) to completion.